The Gordon Research Conference on Macromolecular Organization and Cell Function: Cellular Systems Biology has met biannually. This year the co-chairs of the program are Robert S. Balaban from the NIH and Loranne Agius from the University of Newcastle. The conference continues to focus on internal organization of the living cell to provide a systems level understanding of how interactions between specific molecular constituents contribute to basic cell function. Subcellular organization often is transient, as in the dynamic interactions of molecular motors with the cytoskeleton, of macromolecules in signal transduction pathways, or of the enzymic components of metabolic pathways. Many of these interactions depend on the unique conditions and compartmentation that exist within the intact cell that are disturbed or even destroyed using conventional in vitro approaches. Emphasis is placed on interpretation of biochemical and structural data in the light of known intracellular conditions including the spatial distribution of proteins and metabolites. Discussed are studies on macromolecular assemblies, non-invasive imaging, cellular topology of second messenger signaling pathways, and the global analysis of cellular proteins and metabolites. In addition, theoretical modeling, including the development and testing of mechanisms for handling large amounts of bioinformatics data, is a major emphasis of the conference based on the recognition that complex interactions are very difficult to study without computational tools. The conference is traditionally attended by scientists with a wide range of interests and expertise, ranging from experimentalists to theorists interested in sharing views and approaches. There is active cross-disciplinary discussion that has been greatly stimulating and valuable to the participants, and which has also fostered numerous collaborations.

This year our evening keynote speaker will be Dr. John Scott HHMI Investigator from Oregon Health and Sciences University on the four dimensional aspects of cell signaling in the heart. His lecture is in memory of Dr. Paul Srere. Paul was one of the first scientists to realise the importance of the microenvironment of the protein to its cellular function. Through his major research contributions to this field, Paul was a major driving force in convincing reductionist scientists the importance of studying protein and enzyme function in its correct macromolecular environment rather than through the conventional approaches. The Gordon Conference that Paul started on Macromolecular Organisation and Cell was one of the ways by which this concept developed and gained momentum. This year, as in previous years, we chose the speaker for the closing session with Paul's work and ideas in mind. John Scott has established that cAMP in the cell shows microcompartmentation based on the association of specific isoforms of both adenylate cyclase and cAMP phosphodiesterases with specific binding proteins, thus generating microcompartmentation of cAMP within the cell so that spatially separated pathways can be regulated independently.